The Molecular Targets Center of Biomedical Research Excellence (MT COBRE) at the University of Louisville and the James Graham Brown Cancer Center has successful supported the early career of fourteen junior faculty members during its Phase I and il funding periods. The current application reflects the maturation of the Molecular Targets Program and its faculty. The overall goal of the Phase III application of the Molecular Targets COBRE will be to ensure that the novel targets and compounds which have been identified by MT COBRE faculty are translated to pivotal human clinical trials. Several strengths have enhanced the success of this program including: 1) Stability of program leadership; 2) Successful retention of all fourteen faculty members; 3) Institutional support for the program totaling over $30M; and 4) Creation of a University of Louisville-owned company dedicated to translating important discoveries of MT COBRE investigators. The ability of MT COBRE faculty to test their novel compounds in humans will distinguish this program from similar programs at other institutions.' To this end, the MT COBRE has supported the development of a unique translational research infrastructure which has enabled the characterization of more than 30 novel targets. The Phase III application will support four closely integrated core facilities which will support this goal; 1) Microarray Core; 2) Molecular Modeling Core; 3) NMR/Metabolomic Core and 4) Animal Model Core. Additionally, the James Graham Brown Cancer Center has created complementary research cores which will be available to MT Program members during the Phase III component of the program including the Biostatistics Core, Clinical Trials Office, Biophysical Cancer Core, Cell Sorting and Flow Cytometry Core. The MT COBRE administration will continue to provide intensive support for development of the fourteen faculty members, many of whom have assumed leadership roles within the Cancer Center and University. The robust translational research infrastructure at the James Graham Brown Cancer Center and University of Louisville will ensure the success and sustainability of this unique program.